Novel polyol-glycoside compositions for the skin

ABSTRACT

The invention concerns novel polyol-glycoside compositions for topical use. The invention is characterized in that said compositions contain an efficient amount of polyol-glycoside obtained by acetalization of a polyol of formula (I), wherein n is an integer equal to 2, 3 or 4; or of formula (II), wherein m is an integer equal to 2 or 3, with a reducing sugar. The invention is applicable in cosmetics, dermopharmaceutics, pharmaceutics, textile industry.

The present invention relates to novel polyol-glycoside compositions fortopical use.

The invention is of use preferably in the cosmetics field, but also inthe dermopharmaceutical or pharmaceutical field, in the field of thetextile industry, for example for treating woven or knitted, syntheticor natural textile fibers, or else in the field of the papermakingindustry, for example for manufacturing paper for sanitary or domesticuse.

The expression “for topical use” used in the context of the presentdescription is therefore understood, in its widest sense, to denote anydirect applications (in the case of a cosmetic, dermopharmaceutical orpharmaceutical product) or indirect applications (in the case of textilefibers or of paper) of a composition to the skin or the mucousmembranes.

In its direct applications to the skin, the invention is directed morespecifically toward compositions for improving the integrity of the skinby providing skin comfort.

The expression composition or substance capable of improving the“integrity of the skin” denotes any composition or substance havingmoisturizing properties resulting in particular from an ability toreinforce the epidermal moisture content by promoting in particular thesynthesis of glycosaminoglycans and/or restructuring propertiesresulting in particular from an ability to increase the cellularcohesion of the skin by stimulating the synthesis of epidermalceramides.

It is known that cosmetic compositions generally contain moisturizingsubstances, such as in particular polyols, ethoxylated polyols orhydrolyzed proteins.

Among the polyols, it is glycerol (polyol comprising three hydroxylgroups) which exhibits the highest moisturizing capacity. However, ithas been noted that, at high dose, this can cause certain irritations ofthe skin and of the mucous membranes in particularly sensitiveindividuals.

The search for novel moisturizing substances that are tolerated betterthan glycerol has in particular led to the use of some of itsderivatives such as in particular its acetals resulting fromcondensation with a reducing sugar.

These derivatives which effectively exhibit better skin tolerance thanglycerol are characterized, however, by a moisturizing capacity that isgenerally lower than said glycerol.

Among the glycerol acetals, the products of acetalization of glyceroland of glucose described in document EP 0 770 378 appeared, up untilnow, to provide the best compromise between moisturizing capacity andskin tolerance.

It has been discovered, unexpectedly, and this constitutes the basis ofthe present invention, that the glycosides obtained by acetalization ofcertain polyols containing at least 4, and preferably 4 or 5, hydroxylfunctions exhibit better moisturizing properties than the productsdescribed in document EP 0 770 378, while at the same time havingidentical skin tolerance.

This discovery is all the more surprising for going against apreconceived idea, since those skilled in the art know that themoisturizing capacity of polyols decreases when the number of hydroxylfunctions increases.

In addition, it has been observed, entirely surprisingly, that theabovementioned glycosides exhibit notable restructuring propertiesresulting in particular in a better ability to increase the cellularcohesion of the skin than glycerol.

Thus, according to a first aspect, a subject of the present invention isnovel compositions for topical use, characterized in that they containan effective amount of a polyol-glycoside obtained by acetalization of apolyol of formula:

in which n is an integer equal to 2, 3 or 4; or

in which m is an integer equal to 2 or 3, with a reducing sugar, itbeing understood that the polyol-glycoside is not mannosyl erythritol.

The expression “effective amount” used in the context of the presentapplication signifies an amount that is sufficient to provide thecomposition with a moisturizing and/or restructuring activity on theepidermis.

The polyol-glycosides currently preferred in the context of theinvention are those obtained from a reducing sugar such as, for example:glucose, fructose, galactose, maltose, maltotriose, lactose, cellobiose,mannose, ribose or xylose. Among these compounds, glucose, fructose,galactose, maltose, maltotriose, lactose, cellobiose, ribose and xyloseare more particularly preferred. Among the latter compounds, glucose,xylose and arabinose are most particularly preferred.

Advantageously, the polyol of formula (I) or (II) mentioned above ischosen from erythritol, xylitol and diglycerol.

The xylityl glucoside constitutes the compound that is currentlypreferred in the context of the invention.

The compositions for topical use according to the invention can be usedin many fields.

According to a particular characteristic, these compositions will bechosen from a cosmetic composition, a dermopharmaceutical composition, apharmaceutical composition, and an impregnating composition fortowelettes.

According to a second aspect, a subject of the present invention is theuse of a polyol-glycoside as defined above as an agent for moisturizingthe upper layers of the epidermis, or as an agent for restructuring theepidermis.

The polyol-glycosides, the use of which is recommended according to thepresent invention for preparing compositions for topical use, can beobtained by various synthetic pathways.

A first pathway, referred to as “one-pot synthesis”, consists inintroducing a reducing sugar and a polyol of formula (I) or (II) into areactor, according to a controlled stoichiometric ratio, and insubjecting this mixture to an acetalization reaction under predeterminedtemperature and partial vacuum conditions, in the presence of an acidcatalytic system.

The components of this acid catalytic system will generally be chosenfrom sulfuric acid, hydrochloric acid, phosphoric acid, nitric acid,hypophosphorus acid, methanesulfonic acid, para-toluenesulfonic acid,trifluoromethanesulfonic acid and acid ion exchange resins.

The acetalization reaction will usually be carried out at a temperatureof 70 to 130° C., under a vacuum of 300 to 20 mbar.

A second synthetic pathway consists in:

a) subjecting the polyol of formula (I) or (II) to a dehydration, in thepresence of an acid catalytic system, at a temperature of between 70° C.and 130° C., under partial vacuum, with concomitant elimination of thewater formed during the intramolecular rearrangement undergone by thepolyol; then

b) acetalizing the dehydrated polyol thus obtained, by dispersion of areducing sugar in the reaction medium and by maintenance thereof at atemperature of between 80° C. and 130° C., under partial vacuum.

The acid catalytic system used in this second synthetic pathway may beidentical to that mentioned for the first pathway.

A third synthetic pathway by means of trans-acetalization consists in:

a) preparing butylglucoside by reaction between butanol and glucose inthe presence of an acid catalytic system, at a temperature of between90° C. and 105° C., under partial vacuum, with concomitant eliminationof the water formed during the reaction; and

b) adding a polyol of formula (I) or (II) to the reaction medium thusobtained, with evacuation by distillation under vacuum of the residualbutanol, of the butanol formed during the trans-acetalization reactionand of the water possibly generated during the intramolecularrearrangement of said polyol.

The polyol-glycosides that are useful in the context of the presentinvention are stable and water-soluble products.

Consequently, they can be incorporated into any type of formulationintended for topical use, or alternatively into any type of supportintended to be brought into contact with the skin (paper, towelette,textile, transdermal device, etc.).

In particular, these products can be formulated in the form of asolution, of an emulsion or of a micro-emulsion of the water-in-oil(W/O) or oil-in-water (O/W) type, of a multiple emulsion of thewater-in-oil-in-water (W/O/W) or oil-in-water-in-oil (O/W/O) type, of agel, of an aqueous dispersion, of a solid stick, of an ointment or of anaerosol, or else in anhydrous form, such as a powder.

These products may also be encapsulated, for example in collagennetworks or other usual encapsulation substances, such as, for example,in the form of cellulose encapsulations, in gelatin, in wax matrices orin liposomes.

The polyol-glycosides that are useful in the context of the presentinvention exhibit notable moisturizing properties and make it possiblein particular to reinforce the epidermal moisture content and to promotethe synthesis of glycosaminoglycans.

The polyol-glycosides that are useful in the context of the presentinvention also exhibit notable restructuring properties and make itpossible in particular to increase the cellular cohesion of the skin.Epidermal lipids represent 10 to 12% of the weight of the dry epidermis.They are involved in the permeability of the stratum corneum, in thephenomenon of desquamation and in the regulation of water fluxes in theskin. Ceramides are the essential lipid components of the stratumcorneum, in particular ceramide 1, ceramide 3, ceramide 2, ceramide 4,ceramide 5 and ceramide 6. More precisely, modifications in the amountand in the distribution of the ceramides are observed in a large numberof skin pathologies, in particular those associated with disorders ofkeratinization and of moisturization of the skin: psoriasis, atypicaldermatosis, ichthiosis, Sjogren-Larsson syndrome, xerosis and eczema.

The novel compositions containing the polyol-glycosides that are usefulin the context of the present invention make it possible tosignificantly increase the neosynthesis of epidermal ceramides, moreprecisely of ceramide 1 and of ceramide 2. This increase is surprisingin nature in the sense that it is not observed under identicalexperimental conditions with glycerol.

Consequently, these products may be used in any type of applicationwhere a moisturizing and/or restructuring action on the epidermis isdesired, for example for face or body care. They may also be used inaqueous systems or compositions of surfactants intended for cleansingthe skin and for washing the hair.

The polyol-glycosides that are useful in the context of the presentinvention will generally be used alone or in combination with otheractive principles at a dose of approximately 0.01% to 30% by weight,preferably of 0.1 to 10% by weight, in cosmetic or dermopharmaceuticalformulations having moisturizing and/or restructuring activity.

These formulations may be anti-aging, restructuring, stimulating,free-radical scavenger, antioxidant, anti-dandruff, anti-acne, calming,anti-neuromediator, anti-Substance P, anti-allergic, pain relief,anti-stress, anti-wrinkle, pro-firmness, pro-elasticity, cicatrizing,toning, tensioning, slimming, veinotonic, draining, anti-redness,immunomodulatory, lightening or revitalizing formulae, or else formulaeintended to improve the complexion of the skin, to stimulate the cellsor to promote the synthesis of the proteins of the skin, such ascollagen or keratin.

The formulations having moisturizing and/or restructuring activity onthe epidermis which incorporate a polyol-glycoside according to theinvention may be prepared by the methods conventionally used by thoseskilled in the art in the cosmetology field or in the dermopharmacyfield.

The polyol-glycosides according to the invention are particularly usefulfor tired skin since they introduce the elements necessary for cellulardynamism and for maintaining the functions of the skin. In addition,they stimulate cell regeneration, allowing the skin to become radiantand fresh again.

These polyol-glycosides can also be used in formulae intended to improvecellular exchanges or the condition of the dermal-epidermal junction, orelse in sun products, makeup products, such as lipsticks, rouges,powders, or in products for treating or coloring the hair.

These polyol-glycosides may be combined with all types of adjuvantsnormally used in formulations for topical use, in particular cosmeticsor dermopharmaceutical formulations, such as, for example, fattysubstances, organic solvents, thickeners and gelling agents, softeners,antioxidants, opacifiers, stabilizing agents, foaming agents,fragrances, ionic or nonionic emulsifiers, mineral fillers, sequesteringagents, chelating agents, preserving agents, chemical or mineralscreening agents, essential oils, coloring materials, pigments,hydrophilic or lipophilic active agents, lipid vesicles, etc.

Among the oils which may be combined with these polyol-glycosides,mention may be made of paraffins, isoparaffins, white mineral oils,plant oils, animal oils, synthetic oils, silicone oils and fluoro oils.

Among the other fatty substances that can be combined with theseproducts, mention will be made of fatty alcohols or fatty acids, waxesand butters.

Among the emulsifiers that can be combined with these products, mentionwill be made of the alkyl-polyglycoside- and fatty alcohol-basedcompositions described in patents U.S. Pat. No. 5,958,431, U.S. Pat. No.6,353,034, U.S. Pat. No. 5,888,482, U.S. Pat. No. 6,268,400 and U.S.Pat. No. 5,670,471.

Among the gelling agents or thickeners that can be combined with theseproducts, mention will be made of polymers of natural origin such asxanthan gums, polysaccharides, polymers of synthetic origin such ascarboxyvinyl polymers (Carbomer™), acrylic copolymers, polyacrylamidesor other polymers provided in an inverse emulsion and described inpatents U.S. Pat. No. 6,197,287, U.S. Pat. No. 6,346,239, EP 1 056 805,EP 1 166 771, EP 1 152 023 and EP 1 152 022, polyoxyethylenated sugarderivatives (ethoxylated methylglucose), mixed silicates ofaluminum-magnesium and of sodium-magnesium.

Among the foaming agents that can be combined with these products,mention will be made of betaines, sulfobetaines, alkylpolyglucosides,lipoamino acids, lipopeptides, sodium lauryl ether sulfate, alkylsulfates, alkyl ether sulfates, alkyl ether carboxylates, lipoproteinderivatives, protein derivatives, imidazolines and sulfosuccinates.

Among the active principles that can be combined with the moisturizingpolyol-glycosides of the invention in order to potentiate theirproperties, mention will be made, for example, of any active agentalready exhibiting moisturizing properties, or alternativelypolyphenols, grape extracts, pine extracts, olive extracts (such as forexample Manoliva™), marc extracts, N-acylated proteins, total N-acylatedprotein hydrolysates, amino acids, polyols such as glycerol or butyleneglycol, urea, pyrrolidonecarboxylic acid or a derivative of this acid,glycyrrhetinic acid, alpha-bisabolol, sugars or sugar derivatives,polysaccharides or derivatives thereof, hydroxy acids, vitamins, vitaminderivatives (such as, for example, Sepivital™), enzymes, co-enzymes(such as, for example, Coenzyme Q10™), hormones or “hormone-like”substances (such as, for example, Phytoage™), plant extracts such aswater melon extracts, bogbean extracts, extracts rich in tanins, aquaticmint extracts, soft water or sea water algal extracts, essential waxes,bacterial extracts, minerals such as, for example, mixed potassium andmagnesium aspartate, lipids such as ceramides or phospholipids,hydroquinone, arbutin, kojic acid, active agents having antimicrobialactivity such as Lipacide™ C8G, Lipacide™ UG, Octopirox™, Sensiva™ SC50or Sepicontrol™ A5, the calming active agents described in U.S. Pat. No.6,296,859, active agents having an energizing or stimulant property (forexample Physiogenyl™ or Sepitonic™ M3), panthenol and derivativesthereof (such as Sepicap™ MP), or minerals (Givobio™ range or elseSepitonic™ M3).

The invention will be illustrated through reading the followingnonlimiting examples.

EXAMPLE 1 Method for Preparing Xylityl Glucoside

703.0 g of xylitol are introduced into a glass reactor equipped with ajacket through which circulates a heat transfer fluid, and equipped withan effective stirring device.

The xylitol is melted at a temperature of 135° C., and the viscous pastethus obtained is cooled to 115° C.

Glucose is then added gradually to the reaction medium so as to allow itto disperse homogeneously.

An acid catalytic system consisting of 1.29 g of 96% sulfuric acid isadded to the mixture thus obtained.

The reaction medium is placed under a partial vacuum of 90 mbar to 45mbar, and kept at a temperature of 100° C.-105° C. for a period of 4 h30 min with evacuation of the water formed by means of a distillationassembly.

The reaction medium is then cooled to 95° C.-100° C. and neutralized byadding 5 g of sodium hydroxide at 30%, so as to bring the pH of asolution containing 1% of this mixture to a value of 5.0.

The characteristics of the mixture thus obtained are as follows:

appearance (visual): orange wax at ambient temperature;

pH solution at 1%: 5.0;

residual xylitol: 55.8%;

residual glucose: <1%.

EXAMPLE 2 Method for Preparing Erythrityl Glucoside

300 g of erythritol are introduced into a glass reactor equipped with ajacket through which circulates a heat transfer fluid, and with aneffective stirring device.

The erythritol is melted at a temperature of 145° C.

405 g of additional erythritol are dispersed in the viscous paste thusobtained and kept at 145° C. with stirring.

The reaction medium thus obtained is kept at 135° C.-140° C. for aperiod of 30 min, with stirring, and then 173.4 g of anhydrous glucoseare dispersed in this reaction medium until a fluid and homogeneousmedium is obtained.

The temperature is then brought back to 125° C.-130° C., and a catalyticsystem consisting of 1.61 g of 96% sulfuric acid is then introduced.

The reaction medium is placed under a partial vacuum, of between 45 mbarand 65 mbar, and kept at a temperature of 125° C.-130° C. for a periodof 4 h 30 min with simultaneous evacuation of the water formed by meansof a distillation assembly.

The reaction medium is then cooled to approximately 80° C. andneutralized by adding 6 g of a 30% sodium hydroxide solution so as tobring the pH of a solution containing 1% of this mixture to a value of4.85.

The mixture thus obtained has the following characteristics:

appearance (visual): viscous orangey liquid;

pH of a solution at 1%: 4.85;

residual water: 1.4%;

residual erythritol: 0.4%;

residual glucose: <1%.

COMPARATIVE EXAMPLE Method for Preparing Glyceryl Glucoside

1650.0 g of glycerol are introduced into a glass reactor equipped with ajacket through which circulates a heat transfer fluid, and equipped withan effective stirring device.

The glycerol is brought to 80° C. and 646.0 g of anhydrous glucose aregradually dispersed until a fluid and homogeneous medium is obtained.

The reaction medium is kept at 85° C. for a period of 30 minutes, withstirring, and then 4.65 g of 98% sulfuric acid are introduced.

The reaction medium is then brought to 100° C., placed under a partialvacuum of between 60 and 30 mbar, and maintained for 4 hours withconcomitant evacuation of the water formed in situ by the reaction.

The reaction medium is then cooled to approximately 80° C. andneutralized by adding 24 g of a 30% sodium hydroxide solution so as tobring the pH of a solution containing 1% of this mixture to a value of6.1.

The composition thus obtained has the following characteristics:

appearance (visual): viscous yellow liquid;

pH solution at 1%: 6.1

residual glycerol: 42.4%

residual glucose: <1%

DEMONSTRATION OF THE PROPERTIES OF THE POLYOL-GLYCOSIDES THAT ARE USEFULACCORDING TO THE INVENTION

The moisturizing properties of the polyol-glycosides that are useful inthe context of the invention were demonstrated:

firstly, by in vivo measurement of the moisturization of the skin in anormal volunteer by means of a device known as Hydrascan®; and

secondly, by in vitro measurement of the effect of the polyol-glycosideson the production of hyaluronic acid, a compound of theglycosaminoglycan family capable of attaching up to one thousand timesits weight in water.

A—In Vivo Measurement of the Moisturization of the Skin in a NormalVolunteer by Means of Hydrascan®

The effect on the degree of moisturization of the skin of variouspolyol-glycosides according to the invention, of glyceryl glucoside andof various polyols was measured and compared in humans.

a) Principle of the Method

The degree of moisturization of the skin is measured using the devicesold under the name Hydrascan®.

This device, which is well known to those skilled in the art, makes itpossible to measure transient thermal transfer, a parameter similar tothermal effusivity, which is a property possessed by a body thatexchanges heat with another body with which it is brought into contact.

This device comprises a micro-effusimeter connected to a flexible sensorand makes it possible to produce a thermal wave which propagates withinthe epidermis, and to register the variation in temperature during thepulse.

The setting of the device makes it possible to measure the degree ofmoisturization at three depth levels in the epidermis:

Cycle 1: stratum corneum and superficial epidermis;

Cycle 2: superficial epidermis and middle epidermis;

Cycle 3: the entire epidermis.

The measurements carried out by means of this device therefore make itpossible to explore the superficial layers of the skin and to thusmeasure the degree of moisturization of the skin throughout the entireepidermis.

b) Products Tested

The products tested were formulated in the form of a cream gelcontaining:

3% (weight/volume) of the test product;

2% (weight/volume) of Sepigel® 305 (polyacrylamide/C₁₃-C₁₄isoparaffin/laureth-7);

5% (weight/volume) of Lanol® 99 (isononyl isononanoate);

0.5% (weight/volume) of Sepicide® HB (phenoxy-ethanol, methyl-, ethyl-,propyl-, butylparaben).

A cream gel having the same composition but containing no test productis used as a placebo.

The degree of moisturization of the skin was thus measured and comparedfor the following products:

glucose, xylose, glycerol, xylitol, erythritol, product of example 1,product of example 2, product of the comparative example.

c) Experimental Protocol

The study is carried out on three groups of six volunteers, as adouble-blind study, i.e. neither the experimenter nor the volunteerknows the identity of the test product.

The following four skin zones are defined on the forearms of eachvolunteer:

a zone treated with a polyol-glucoside;

a zone treated with the corresponding polyol;

a zone treated with the placebo common to all the products;

an untreated zone.

The products are applied topically at a rate of 20 mg/cm², themeasurements being carried out 8 h after application.

To avoid undesirable variations in the measurements, the volunteers areplaced in a temperature-controlled (25° C.±2° C.) andhygrometry-controlled (50%±4%) room for at least 30 min.

The degree of moisturization is measured by means of Hydrascan®, on eachskin zone defined above, the values obtained for each of the threecycles being recorded and expressed as percentage increase inmoisturization of the skin relative to the zone treated with theplacebo. These values correspond to the mean obtained for the sixvolunteers.

d) Results Obtained Degree of moisturization of the skin measured withHydrascan ® Cycle 1: Cycle 2: stratum corneum + superficial + Cycle 3:superficial middle entire Product epidermis epidermis epidermis Glucose<5% <5% <5% Xylose <5% <5% <5% Glycerol (3 OH) +14% +13% +13% Erythritol(4 OH) +9% +9% +9% Xylitol (5 OH) <5% <5% <5% Comparative example <5%<5% <5% Example 2 +18% +11% +12% Example 1 +28% +33% +30%e) Analysis of the Results—Conclusions

The results, reported in the above table, show that glycerol increasesthe degree of moisturization of the superficial and middle layers of theepidermis and also of the entire epidermis. The increase is comparablewhatever the epidermal layer studied.

On the other hand, this increase is very substantially reduced when theglycerol is etherified with glucose (product of the comparativeexample).

Glucose and xylose alone exhibit no moisturizing effectiveness.

The xylitol (polyol having five hydroxyl groups) has no effect on thedegree of moisturization of the various layers of the epidermis. On theother hand, the xylityl glucoside (product of example 1) verysubstantially increases the degree of moisturization of the superficialand middle layers of the epidermis and also of the entire epidermis. Theincrease is greater, of the order of 14 to 20%, than that obtained withglycerol.

Erythritol (polyol having four hydroxyl groups) increases the degree ofmoisturization of the superficial and middle layers of the epidermis andalso of the entire epidermis. However, the effect is less substantialthan that obtained with glycerol. On the other hand, this increase isamplified when the erythritol is in the form of erythrityl glycoside(product of example 2).

In conclusion, this study:

shows the moisturizing capacity of glycerol and of erythritol andconfirms that this moisturizing capacity decreases when the number ofhydroxyl groups of the polyol increases;

demonstrates the very strong moisturizing potential of the xylitylglucoside and, to a slightly lesser degree, that of the erythritylglucoside. These two moisturizing potentials are greater than that ofthe glycerol and of the glyceryl glucoside.

B—In Vitro Measurement of the Effect of the Polyol-Glycosides Accordingto the Invention on the Production of Hyaluronic Acid

To confirm the moisturizing activity of the polyol-glycosides accordingto the invention, the effect of these products on the amount ofhyaluronic acid was measured. It is in fact known that hyaluronic acidis a major non-sulfated glycosaminoglycan which plays an essential rolein moisturizing the skin, by means of its ability to attach up to 1000times its weight in water.

a) Principle of the Method

The amount of hyaluronic acid is measured in normal human dermalfibroblast cultures.

The cells are incubated for 5 days in the presence of the test productssolubilized in the incubation medium.

At the end of this incubation, the extracellular media, into which thehyaluronic acid is secreted, are removed.

The hyaluronic acid is stained with a specific dye, STAINS ALL((1-ethyl-2-[3-(1-ethylnaphtho[1,2-d]thiazolin-2-ylidene)-2-methylpropenyl]naphtho[1,2-d]thiazolium)bromide, provided by Sigma), which interacts with the hyaluronic acid toproduce a change of absorption spectrum between 620 and 660 nm, observedby means of a spectrophotometer. A standard range of hyaluronic acid iseffected in parallel.

b) Products Tested

The polyols and the polyol-glucosides are tested in aqueous solution at0.01% and 0.1% (w/v).

The polyols tested are glycerol, xylitol and erythritol. Thepolyol-glucosides tested are glyceryl glucoside (product of thecomparative example), xylityl glucoside (product of example 1) anderythrityl glucoside (product of example 2).

c) Experimental Protocol:

This can be summarized by means of the following diagram:

in which D0, D3 and D8 have the following meanings:

D0: seeding of the fibroblasts (24-well culture plates, 15 300cells/well);

D3: incubation of the products tested, diluted in the fibroblastincubation medium;

D8: removal of the fibroblast incubation media, assaying of thehyaluronic acid.

At the end of the 5 days of incubation in the presence of the products,the incubation media are removed and incubated in the presence of STAINSALL. The colorimetric reaction is visualized by adding water.

The quantification is carried out by spectrophotometry for a wavelengthof 630 nm.

A standard range of hyaluronic acid (0 to 12.5 μg/ml) is effected inparallel.

The results are expressed in μg/ml of extracellular hyaluronic acid.

d) Results Obtained:

The results which were obtained, expressed as percentage increase in theamount of extracellular hyaluronic acid relative to the control group,are reported in the following table: Concentration (%, w/v) Product 0.010.1 Glucose <10% <10% Glycerol <10% <10% Erythritol <10% <10% Xylitol<10% <10% Product of the comparative example <10% <10% Product ofexample 2 +64% <10% Product of example 1 +158% +161%e) Analysis of the Results—Conclusions

After 5 days of incubation in the presence of the fibroblasts, none ofthe polyols tested increases the amount of extracellular hyaluronicacid.

The glyceryl glucoside (product of the comparative example) does notincrease the amount of extracellular hyaluronic acid.

The xylityl glucoside (product of example 1), and to a lesser degree,the erythrityl glucoside (product of example 2), increase the amount ofextracellular hyaluronic acid.

Among the three polyol-glucosides tested, the xylityl glucoside (productof example 1) is the most effective.

The three polyols tested, glycerol, xylitol and erythritol, have noeffect on the extracellular amount of hyaluronic acid.

Among the three polyol-glucosides tested, glyceryl glucoside, xylitylglucoside and erythrityl glucoside, the xylityl glucoside very markedlyincreases the extracellular amount of hyaluronic acid. The erythritylglucoside also increases this parameter, to a less substantial degree.This in vitro model makes it possible to select the xylityl glucoside asbeing the most advantageous product; this classification is similar tothat obtained in the in vivo test.

The restructuring properties of the polyol-glycosides that are useful inthe context of the invention were demonstrated by in vitro measurementof the effect of the polyol-glycosides, in particular the xylitylglucoside, on the synthesis of ceramide 1 and ceramide 2, which arecompounds of the family of epidermal lipids which play a key role in thebarrier function of the skin.

C—In Vitro Measurement of the Xylityl Glucoside According to theInvention on the Synthesis of Epidermal Ceramides

To illustrate the increase in cellular cohesion of the skin by means ofthe polyol-glycosides, in particular by means of the xylityl-glucosideaccording to the invention, the effect of these products on thesynthesis of ceramide 1 and of ceramide 2 was measured in comparisonwith glycerol and compounds known by those skilled in the art toincrease this synthesis.

a) Principle of the Method

The study is carried out in vitro in a human skin explant model. Theproducts, formulated at 3% in a cream gel, are applied to the surface ofthe skin explants for 24 hours. The neosynthesis of the epidermal lipidsis studied by radioactive labeling (carbon 14-labeled acetate) of theneosynthesized lipids, followed by thin layer chromatography to separatethe various types of lipids and in particular the ceramides.

b) Products Tested

The xylityl glucoside according to example 1 of the invention,formulated at 3% in a cream gel comprising 2% of Sepigel® 305, 5% ofLanol 99, and qs of water.

Glycerol formulated at 3% in the same cream gel.

Epidermal growth factor (EGF), known to increase the synthesis ofceramides, which constitutes a reference molecule for this test.

The EGF is tested at 10 ng/ml in the skin explant culture medium.

A placebo corresponding to the cream gel.

A commercially available formulation containing lactic acid, whichconstitutes a reference for the test, lactic acid being known toincrease the synthesis of ceramides.

c) Experimental Protocol

The study is carried out on disks of human skin originating fromcosmetic surgery (abdominoplasty, 35-year-old caucasian woman). Disks 8mm in diameter are produced using a hole punch and deposited ontoculture inserts placed in culture wells containing an appropriatenutritive medium (MEM/M199 medium (¾, ¼, v/v) supplemented withpenicillin (50 IU/ml, streptomycin (50 μg/ml), sodium bicarbonate (0.2%w/v), serum (2% v/v) and carbon 14-labeled acetate (1 μCi/ml)).

The products are tested by topical application (except for the EGF) for24 hours.

At the end of the 24 hours of incubation, the skin explants are rinsedwith phosphate buffered saline. For each disk of skin, the dermis isdissociated from the epidermis by controlled heat shock (1 min at 70°C.). The epidermal lipids are extracted by a partition between anorganic phase (methanol/chloroform (1:2)) and an aqueous phase (0.25 Mpotassium chloride). The organic phase is then evaporated under vacuumand the residue is taken up in a chloroform/methanol (2:1) mixture.

The various epidermal lipids are then separated by thin layerchromatography (silica 60): chloroform/acetone/methanol (38:2:10);chloroform/acetone/methanol (40:5:5); chloroform/ethyl acetate/diethylether/methanol (36:10:3:1). The radioactivity of the fractions thusseparated is counted with a radioactivity analyzer (Storm, Amersham).

The results are expressed as % variation relative to the control group.

d) Results Obtained

The results which were obtained, expressed as percentage increase in theamount of ceramide 1 and of ceramide 2 relative to the control group,are reported in the following table: Xylityl Formulation glucoside withlactic according to EGF acid example 1 Glycerol Placebo Ceramide 1166.1% 158.5% 295.7% 114.9% 174.6% Ceramide 2 152.3% 125.6% 236.5%151.7% 169.9%e) Analysis of the Results—Conclusion

The use of the xylityl glucoside in the cream gel significantlyincreases the neosynthesis of ceramides 1 and 2, which is not observedin the presence of glycerol or of the placebo in the same formulationscheme.

The EGF and the formulation containing lactic acid, known by thoseskilled in the art to possess an action on the increase in neosynthesisof ceramides 1 and 2, act, but less effectively than the compositionderived from example 1 of the invention.

These effects on the ceramides reflect a restructuring effect of thexylityl glucoside on the skin barrier, which is, moreover, in agreementwith the moisturization measurements carried out in vivo in the variouslayers of the epidermis. These results are in agreement with long-termmoisturizing effects of the xylose-glucoside.

DEMONSTRATION OF THE SKIN TOLERANCE OF THE POLYOL-GLYCOSIDES THAT AREUSEFUL ACCORDING TO THE INVENTION

The skin tolerance of the various polyol-glycosides was evaluated bymeans of a study of “evaluation on the skin of acute skin irritation”,carried out by an independent pharmaceutical and cosmeticconsultancy-expertise company.

The Primary Cutaneous Irritation (PCI) index measurements, carried outaccording to the same protocol, are contained in the following table:IRRITATION Product PCI index Classification Xylityl glucoside 0Nonirritant (example 1) Erythrityl glucoside 0 Nonirritant (example 2)Glyceryl glucoside 0 Nonirritant (comparative example)

Each compound studied is classified, in view of the results obtainedunder the selected experimental conditions, nonirritant for the skin,with reference to the scale proposed in the protocol described in theJournal Officiel de la République Francaise [Official Journal of theFrench Republic] of Feb. 21, 1982.

These novel polyol-glycoside compositions (examples 1 and 2) do nottherefore induce any modification in skin tolerance compared with thecomparative example relating to a prior state of the art.

Some examples of compositions having moisturizing activity according tothe invention will now be given.

EXAMPLE 3 Moisturizing Body Milk

Formula A Water QS   100% Fucogel 03.00% Micropearl ™ M305 (methylmethacrylate cross- 05.00% polymer) Moisturizing active agent 03.00%Montanov ™ L (C₁₄-C₂₂ alcohol & C₁₂-C₂₀ alkyl 04.00% glucoside) BLanol ™ 99 (isononyl isononanoate) 04.00% Simulgel ™ EG (sodium acrylatesodium acryloyl- 01.00% dimethyl taurate copolymer/isohexadecane/sorbitan oleate) C DC345 (cyclomethicone) 12.00% D Fragrance qs.Sepicide ™ HB (phenoxyethanol/methylparaben/ 00.30%ethylparaben/propylparaben/butylparaben) Sepicide ™ CI (imidazolidinylurea) 00.20%Procedure:

the fatty and aqueous phases (B and A) are heated separately to 75°C.-80° C.,

B is emulsified in A with stirring by means of a rotor-stator turbine,

C is added and the mixture is maintained for a few minutes with vigorousstirring,

the mixture is cooled with moderate stirring,

D is added at 30° C.

EXAMPLE 4 Moisturizing Cream-Gel

Formula A Water qs 100% Glycerol 02.50% Micropearl ™ M305 01.00%Sepicide ™ CI 00.20% Moisturizing active agent 02.00% B Simulgel ™ EG01.00% C Lanol ™ 99 05.00% DC345 02.50% Sepicide ™ HB 00.30% Fragranceqs.Procedure:

the Micropearl™ M305 is dispersed at ambient temperature in thewater/glycerol/moisturizing active agent/Sepcide™ CI mixture,

phase A prepared according to the method mentioned above is added to Bgradually, homogenizing the preparation after each addition withmoderate stirring,

C is added to the gel prepared above.

Characteristics: Appearance: brilliant white gel; pH=6.2.

EXAMPLE 5 Moisturizing Energizing Body Water

Formula: A Fragrance qs. Oramix ™ CG 110 02.50% Sepicide ™ HB 00.50% BGlycerol 01.00% Moisturizing active agent  1.00% Sepitonic ™ M3 01.00%Sepicide ™ CI 00.30% Water qs. 100%Procedure:

the fragrance and the Sepicide™ HB are solubilized in the Oramix™ CG 110in order to prepare A,

the ingredients of B are added in the order indicated at ambienttemperature with moderate stirring.

Characteristics: Appearance: clear translucent and colorless liquid;pH=5.

EXAMPLE 6 Energizing Shower Gel

Formula A Moisturizing active agent 03.00% Sepicide ™ HB 00.30%Fragrance qs. Montanox ™ 81 (polysorbate 81) 02.00% B Proteol ™ OAT(sodium lauroyl OAT amino 05.00% acids) 28% sodium lauryl ether sulfate45.00% Sepitonic ™ M3 01.00% Sepicide ™ CI 00.30% Water qs. 100%Montaline ™ C40 (cocamidopropylalbetainamide 05.00% MEA chloride) Sodiumchloride 00.75% Lactic acid qs. pHProcedure:

the ingredients of phase A are mixed at ambient temperature withmoderate stirring,

the ingredients of phase B are added in the order indicated, under thesame operating conditions.

Characteristics: Appearance: clear gel; pH=6.5.

EXAMPLE 7 Moisturizing Lipstick

Formula: A Castor oil qs. 100.00% Cera alba (beeswax) 07.50% Candellilawax 07.50% Cera microcristallina 15.00% Sepifeel ™ One(palmitoylproline/magnesium 03.00% palmitoyl glutamate/sodium palmitoylsarcosinate-Seppic) Sepilift ™ DPHP (DiPalmitoylHydroxyProline- 01.00%Seppic) Cetyl alcohol 01.50% Isopropyl lanolate 01.00% Cetyl ricinoleate00.80% Micropearl ™ M 310 (crosslinked PMMA, 02.00% distributed bySeppic) Butyrospermum parkii (karite butter) 03.00% Paraffinum liquidum02.50% Lanol ™ 1688 (cetearyl octanoate - Seppic) 02.50% Caprylic/caprictriglyceride 04.00% Carnauba wax 03.50% CI 77491 01.40% CI 45410-DC red27 00.10% CI 77891-titanium dioxide 11.00% Perfluoromethyl isopropylether 00.10% B Montane ™ 80 47.50% Water qs. 100.00% Moisturizing activeagent 05.00% Sepicide ™ CI 00.20% Sepicide ™ HB 00.30%Procedure:

phase A is prepared in a three-cylinder mill, by adding each compound,prepared beforehand, in molten form,

phase B is added at 80° C. with moderate stirring, until a homogeneousdispersion on the molten phase is obtained,

the mixture is then poured into molds suitable for the molding.

1-15. (canceled)
 16. A composition which may be used topically, saidcomposition comprising non-mannosyl erythritol polyol-glycoside, whereinsaid polyol-glycoside is obtained by the acetalization of a polyol witha reducing sugar, wherein said polyol comprises at least one memberselected from the group consisting of: a) a polyol with the formula:

wherein n is 2, 3 or 4; and b) a polyol with the formula:

wherein m is 2 or
 3. 17. The composition of claim 16, wherein saidreducing sugar comprises at least one member selected from the groupconsisting of: a) glucose; b) fructose; c) galactose; d) maltose; e)maltotriose; f) lactose; g) cellobiose; h) mannose; i) ribose; and j)xylose.
 18. The composition of claim 17, wherein said reducing sugarcomprises at least one member selected from the group consisting of: a)glucose; b) fructose; c) galactose; d) maltose; e) maltotriose; f)lactose; g) cellobiose; h) ribose; and i) xylose.
 19. The composition ofclaim 18, wherein said reducing sugar comprises at least one memberselected from the group consisting of: a) glucose; b) xylose; and c)arabinose.
 20. The composition of claim 16, wherein said polyolcomprises at least one member selected from the group consisting of: a)erythritol; b) xylitol; and c) diglycerol.
 21. The composition of claim16, wherein said polyol-glycoside comprises xylityl glucoside.
 22. Thecomposition of claim 16, wherein said composition comprises at least onemember selected from the group consisting of: a) a cosmetic composition;and b) a pharmaceutical composition.
 23. The composition of claim 22,wherein said composition comprises a dermopharmaceutical composition.24. The composition of claim 16, wherein said composition is in a formcomprising at least one member selected from the group consisting of: a)a solution; b) a water-in-oil (W/O) emulsion; c) an oil-in-water (O/W)emulsion; d) a water-in-oil (W/O) microemulsion; e) an oil-in-water(O/W) microemulsion; f) a water-in-oil-in-water (W/O/W) multipleemulsion; g) an oil-in-water-in-oil (O/W/O) multiple emulsion; h) a gel;i) an aqueous dispersion; j) a solid stick; k) an ointment; l) anaerosol; and m) an anhydrous form.
 25. The composition of claim 24,wherein said anhydrous form comprises a powder.
 26. The composition ofclaim 24, wherein said form is for impregnating towelettes.
 27. A methodof moisturizing the upper layers of the epidermis with a composition,wherein said composition comprises a non-mannosyl erythritolpolyol-glycoside, wherein said polyol-glycoside is obtained by theacetalization of a polyol with a reducing sugar, wherein said polyolcomprises at least one member selected from the group consisting of: a)a polyol with the formula:

wherein n is 2, 3 or 4; and b) a polyol with the formula:

wherein m is 2 or
 3. 28. The method of claim 27, wherein said reducingsugar comprises at least one member selected from the group consistingof: a) glucose; b) fructose; c) galactose; d) maltose; e) maltotriose;f) lactose; g) cellobiose; h) mannose; i) ribose; and j) xylose.
 29. Themethod of claim 28, wherein said reducing sugar comprises at least onemember selected from the group consisting of: a) glucose; b) fructose;c) galactose; d) maltose; e) maltotriose; f) lactose; g) cellobiose; h)ribose; and i) xylose.
 30. The method of claim 29, wherein said reducingsugar comprises at least one member selected from the group consistingof: a) glucose; b) xylose; and c) arabinose.
 31. The method of claim 30,wherein said polyol comprises at least one member selected from thegroup consisting of: a) erythritol; b) xylitol; and c) diglycerol. 32.The method of claim 31, wherein said polyol-glycoside comprises xylitylglucoside.
 33. A method for restructuring the epidermis with acomposition, wherein said composition comprises a polyol-glycoside,wherein said polyol-glycoside is obtained by the acetalization of apolyol with a reducing sugar, wherein said polyol comprises at least onemember selected from the group consisting of: a) a polyol with theformula:

wherein n is 2, 3 or 4; and b) a polyol with the formula:

wherein m is 2 or
 3. 34. The method of claim 33, wherein said reducingsugar comprises at least one member selected from the group consistingof: a) glucose; b) fructose; c) galactose; d) maltose; e) maltotriose;f) lactose; g) cellobiose; h) mannose; i) ribose; and j) xylose.
 35. Themethod of claim 34, wherein said reducing sugar comprises at least onemember selected from the group consisting of: a) glucose; b) fructose;c) galactose; d) maltose; e) maltotriose; f) lactose; g) cellobiose; h)ribose; and i) xylose.
 36. The method of claim 35, wherein said reducingsugar comprises at least one member selected from the group consistingof: a) glucose; b) xylose; and c) arabinose.
 37. The method of claim 36,wherein said polyol comprises at least one member selected from thegroup consisting of: a) erythritol; b) xylitol; and c) diglycerol. 38.The method of claim 37, wherein said polyol-glycoside comprises xylitylglucoside.